The role of p21 Waf1/Cip1 in large airway epithelium in smokers with and without COPD

Giuseppina Chiappara, Mark Gjomarkaj, Alessia Virzì, Serafina Sciarrino, Maria Ferraro, Andreina Bruno, Angela Marina Montalbano, Patrizio Vitulo, Marta Ida Minervini, Loredana Pipitone, Elisabetta Pace

Research output: Contribution to journalArticlepeer-review

Abstract

Airway epithelium alterations, including squamous cell metaplasia, characterize smokers with and without chronic obstructive pulmonary disease (COPD). The p21 regulates cell apoptosis and differentiation and its role in COPD is largely unknown. Molecules regulating apoptosis (cytoplasmic p21, caspase-3), cell cycle (nuclear p21), proliferation (Ki67/PCNA), and metaplasia (survivin) in central airways from smokers (S), smokers-COPD (s-COPD) and non-smokers (Controls) were studied. The role of cigarette smoke extracts (CSE) in p21, survivin, apoptosis (caspase-3 and annexin-V binding) and proliferation was assessed in a bronchial epithelial cell line (16HBE). Immunohistochemistry, image analysis in surgical samples and flow-cytometry and carboxyfluorescein succinimidyl ester proliferative assay in 16HBE with/without CSE were applied. Cytoplasmic and nuclear p21, survivin, and Ki67 expression significantly increased in large airway epithelium in S and in s-COPD in comparison to Controls. Caspase-3 was similar in all the studied groups. p21 correlated with epithelial metaplasia, PCNA, and Ki67 expression. CSE increased cytoplasmic p21 and survivin expression but not apoptosis and inhibited the cell proliferation in 16HBE. In large airway epithelium of smokers with and without COPD, the cytoplasmic p21 inhibits cell apoptosis, promotes cell proliferation and correlates with squamous cell metaplasia thus representing a potential pre-oncogenic hallmark.

Original languageEnglish
Pages (from-to)1473-1481
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1832
Issue number10
DOIs
Publication statusPublished - Oct 2013

Keywords

  • Apoptosis
  • COPD
  • Epithelium
  • Metaplasia
  • Proliferation

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

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